1. Field of the Invention
The present invention relates to the preparation and use of novel estratriene and estratetraene compositions bearing a dicarbadodecaboranyl substituent at the 17-position useful in the destruction of cancerous cells containing estrogen receptors by boron-neutron capture therapy.
2. Description of the Prior Art
It is known that the non-radioactive boron isotope (.sup.10.sub.5 B), on capture of a low-energy thermal neutron, emits a 2.33 MeV short-range alpha particle that is fatal to cells in a reaction that may be depicted as follows: EQU .sup.10.sub.5 B+.sup.1.sub.0 n.fwdarw..sup.7.sub.3 Li+.sup.4.sub.2 He+2.33 MeV
Therefore, if .sup.10.sub.5 B nuclei of sufficiently high concentration are imbedded in cancerous cells and irradiated with thermal neutrons, cancerous tissues may be selectively destroyed.
Prior art methods for boron neutron capture therapy in the treatment of tumors suffered from a number of deficiencies. Many boron compounds which were tested in thermal neutron therapy failed to be stable in vivo, were toxic, or were non-tumor specific.
It has been suggested that estrogen compounds containing .sup.10.sub.5 B nuclei would be useful in the treatment of cancers which are localized in areas bearing estrogen receptors, such as cancer of the breast, uterus and endometrium. For example, Sweet (Steroids 37, 223-238 (1981)) described the preparation of "estradiol-17.beta. 3-carboranylmethyl ether". However, Sweet's compound had very low uterotopic and estrophilic activity, and therefore, it is not useful in the destruction of cancerous tissue containing estrogen receptors.
It is therefore an object of this invention to produce estratriene and estratetraene compositions bearing a dicarbadodecaboranyl substituent at the 17-position useful for boron neutron capture therapy of cancerous tissues. It is a further object of this invention to produce estratriene and estratetrane compositions bearing a dicarbadodecaboranyl substituent at the 17-position which are stable in vivo, and which possess high uterotropic and estrophilic activity.